Project description:A porcine aortic coarctation model was used to examine regulation of gene expression in early hypertensive vascular remodeling. Aortic segments were collected proximal (high pressure) and distal (low pressure) to the coarctation after 2 weeks of sustained hypertension (mean arterial pressure>150mmHg). Porcine 10K oligoarrays used for gene expression profiling of the two regions of aorta revealed downregulation of cytoskeletal and upregulation of extracellular region genes relative to the whole genome. A genomic database search for transforming growth factor-β (TGFβ) control elements (TCE) showed that 19% of the genes that changed expression due to hypertension contained putative TCEs. Real time PCR and microarray analysis showed no change in expression of TGFβ1, TGFβ2, TGFβ3, or bone morphogenetc proteins (BMP)2 and 4, yet immunohistochemical staining for phosphorylated SMAD2, an indicator of TGFβ signaling, and for phosphorylated SMAD1/5/8, an indicator of signaling through the BMPs, showed the highest percentage of positively stained cells in the proximal aortic segments of occluded animals. For TGFβ signaling, this increase was significantly different from sham-operated controls. Western blot analysis showed no difference in total TGFβ1 protein levels with respect to treatment or aortic segment. Immunohistochemistry showed that the protein levels of latency associated peptide, was decreased in proximal segments of occluded animals. Collectively, these results suggest that activation of TGFβ, but not altered expression, may be a major mechanism regulating early hypertensive vascular remodeling.
Project description:T Cell Receptor Based Therapy of Metastatic Colorectal Cancer With mRNA-engineered T Cells Targeting Transforming Growth Factor Beta Receptor Type II (TGFβII)
Project description:Systematic in vitro and in vivo characterization of Leukemia-inhibiting factor (LIF)- and Fibroblast growth factor (FGF) -derived porcine induced pluripotent stem cells (piPSC) vs. embryonic stages
Project description:Transforming Growth Factor-β (TGFβ) Prevents Hypertensive Aortic Dissection in Adult Mice via Extracellular Matrix Production (Bulk KO vs. WT Aorta)
Project description:Regulatory Mechanisms of Atrial Remodeling of Mitral Regurgitation Pigs This study enrolled 6 pigs (age: 18 months) and divided into three groups: mitral regurgitation pigs (MR) (n = 2; 2 males sacrificed 12 months after surgery), MR pigs treated with valsartan (MRV) (n = 2; 2 males age-matched to MR sacrificed 12 months after surgery), and normal control pigs (NC) (n = 2; 2 males age-matched to MR pigs). Valsartan (3.43 mg/kg/day), a type I angiotensin II receptor blocker, was administered from one week before surgery and then daily after surgery in the MRV group. We sought to systemically elucidate critical differences in the alteration of RNA expression pattern between the atrial myocardium of pigs with and without MR, and between the atrial myocardium of MR pigs with and without valsartan using high-density oligonucleotide microarrays and functional network enrichment analysis.
Project description:To determine whether the novel Proprotein Convertase Subtilisin/Kexin Type 9(PCSK9-RRB- inhibitor inkslan has renal protective effects in high glucose environments, we tested the effectsInkslanslan on renal function in rats, proteomics technology was used to predict whether its effects were related through the Transforming Growth Factor-β (TGF-β) pathway, and to construct its regulatory network. The Transforming Growth Factor of Transforming Growth Factor-β (TGF-β) pathway was analyzed
